Liver Complications In Patients Research Articles

Severe Fontan-Associated Liver Disease and Its Association With Mortality.

Background Data are rare about the incidence of severe Fontan-associated liver disease (FALD) and its association with mortality. We sought to: (1) estimate the probability of developing severe FALD in patients who undergo the Fontan procedure (Fontan patients), compared with severe liver complications in patients with a ventricular septal defect; (2) assess the severe FALD-mortality association; and (3) identify risk factors for developing severe FALD. Methods and Results Using the Quebec Congenital Heart Disease database, a total of 512 Fontan patients and 10 232 patients with a ventricular septal defect were identified. Kaplan-Meier curves demonstrated significantly higher cumulative risk of severe FALD in Fontan patients (11.95% and 52.24% at 10 and 35 years, respectively), than the risk of severe liver complications in patients with a ventricular septal defect (0.50% and 2.75%, respectively). At 5 years, the cumulative risk of death was 12.60% in patients with severe FALD versus 3.70% in Fontan patients without FALD (log-rank P=0.0171). Cox proportional hazard models identified significant associations between the development of severe FALD and congestive heart failure and supraventricular tachycardia, with hazard ratios (HRs) of 2.36 (95% CI, 1.38-4.02) and 2.45 (95% CI, 1.37-4.39), respectively. More recent Fontan completion was related to reduced risks of severe FALD, with an HR of 0.95 (95% CI, 0.93-0.97) for each more recent year. Conclusions This large-scale population-based study documents that severe FALD in Fontan patients was associated with a >3-fold increase in mortality. The risk of FALD is time-dependent and can reach >50% by 35 years after the Fontan operation. Conditions promoting poor Fontan hemodynamics were associated with severe FALD development.

A254 HEPATIC SEQUELAE OF POST-ACUTE COVID-19 SYNDROME (PACS): A SYSTEMATIC REVIEW OF THE CURRENT LITERATURE

Abstract Background Post-acute COVID-19 syndrome (PACS), colloquially known as long-COVID, is a syndrome characterized by persistent or delayed symptoms four weeks or beyond from initial infection onset. Observational studies have shown liver injury during acute COVID-19 infection, particularly in severe infections requiring hospitalization. This has been observed in forms of increased liver enzyme markers, imaging, fibrosis and transplant rejection. However, the data on resolution of abnormal liver injury markers is inconsistent. As such, the long-term hepatic sequelae following acute COVID-19 infection remains unclear. Purpose To assess the current understanding of long-term hepatic sequalae of COVID-19 in adults, and to identify prevalence and odds of liver complications in patients with PACS compared to COVID-negative individuals. Method Included criteria consisted of observational or cross-sectional studies with patients ≥18y at least four weeks following COVID-19 infection evaluating liver disease/involvement. Liver involvement was defined as per primary study, in order to accomodate various modalities of hepatic injury (e.g. lab markers, imaging, etc.). Case reports or series, systematic reviews, literature reviews, meta-analyses, editorials and commentaries were excluded, as well as studies that report liver function/injury only during acute COVID-19 infection rather than following. Systematic searches were performed on MEDLINE, CINAHL and EMBASE. All studies were screened by two independent reviewers. Risk of bias was assessed by two independent reviewers using the Cochrane ROBIN-E tool. All conflicts from screening, data extraction and risk of bias assessment stages were resolved by a third independent reviewer. Data on biochemical liver markers, imaging, fibrosis and clinical scores were collected where available. Result(s) 2734 studies were found and 614 duplicates were removed. 2117 abstracts and 35 subsequent full texts were screened. Most studies were high or very high risk of bias; only two studies were found to be low risk of bias. Only nine studies utilized control groups. Most studies assessed liver enzymes. 22 of 26 studies suggested some type of abnormality in hepatic testing following COVID-19 infection. 14 studies suggested persistently abnormal liver function tests in PACS patients. 5 studies suggested persistent imaging, fibrosis or autopsy abnormalities. Given the high risk of bias, meta-analysis could not be reliably performed among all included studies. Conclusion(s) Despite most studies suggesting there is a proportion of patients who suffer from prolonged liver abnormalities such as elevated liver enzymes or fibrosis on imaging, the reliability of these fundings is uncertain given high risk of bias and lack of consistent control groups. As such, there is insufficient high-quality data to inform the natural history of hepatic sequalae following COVID-19 infection. Further high-quality research is required in this field to inform future clinical decisions. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Liraglutide on type 2 diabetes mellitus with nonalcoholic fatty liver disease: A systematic review and meta-analysis of 16 RCTs.

Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity of type 2 diabetes mellitus (T2DM). Our aim is to investigate the effects of liraglutide on T2DM with NAFLD. Relevant articles published from the earliest publication to March 2022 were selected from several databases. The Cochrane Collaboration's RevMan software was used for the analysis. Sixteen studies are selected for this meta-analysis, which includes totally 634 patients in the treatment group and 630 patients in the control group. As a result, 14 studies show that fasting plasma glucose levels of the experimental group are lower than that of the control group; 15 studies show that glycosylated hemoglobin A1c levels of the experimental group are lower than that of the control group; 13 studies show that triglyceride levels of the experimental group are lower than that of the control group; twelve studies show that total cholesterol levels of the experimental group are lower than that of the control group; 10 studies show that alanine aminotransferase levels of the experimental group is lower than that of the control group; 10 studies show that no significant difference in changes in aspartate transaminase between 2 groups; 13 studies show that low density lipoprotein cholesterol levels of the experimental group is lower than that of the control group; 9 studies show that no significant difference in changes in high density lipoprotein cholesterol between 2 groups; 7 studies mentioned adverse effects and the difference is significant. Liraglutide is potentially curative for T2DM with NAFLD.

Gastrointestinal and Liver Complications in Patients with Diabetes Mellitus-A Review of the Literature.

The number of diabetes mellitus patients has increased over the last few years in developing countries, along with obesity and sedentary lifestyle. Besides macroangiopathy and microangiopathy, damage to the nerve fibers of the peripheral nervous system is the most common chronic complication of diabetes. Digestive complications in diabetic patients represent a consequence of diabetic autonomic neuropathy involving the gastrointestinal tract, but unfortunately not always evaluated by diabetologists. Aside from the complications encountered in the digestive tract, patients with diabetes mellitus are prone to developing liver diseases. This review will describe the prevalence of these complications, the modality of diagnosis, and therapeutical solutions in order to reduce the risk of progression of these complications in diabetic subjects.

Antipsychotics and mood stabilizers on risk for hepatic failure in people with schizophrenia and bipolar disorder

IntroductionPatients with severe mental disease have a considerably shorter lifespan than the general population. The majority of psychiatric drugs are metabolized by the liver. Cytochromes play a central role, interactions between drugs are expected. Neuroleptics are frequently associated with weight gain, steatosis development, elevation of liver enzymes and rare acute cytolytic hepatitis, particularly with clozapine and olanzapine. Mood stabilizers, like Valproate classically gives mitochondrial steatosis with potentially important damages, and also possible acute liver failure.ObjectivesThis case presents a 56-year-old patient, previously diagnosed of schizoaffective disorder, with chronic psychotic symptoms that showed high drug resistance. She had been treated in the past with most common antipsychotic drugs with no clinical response. While being in treatment with valproate and olanzapine, she was started on clozapine while olanzapine removed. Two weeks later she developed Acute Pharmacologic Hepatitis with mild liver failure.MethodsPhysical examination was normal. Mental exam revealed presence of delusion. Blood tests showed: hyperbilirubinemia and mil coagulopathy. Clozapine dose was reduced and valproate was suspended.ResultsThe patient showed a substantial improvement of hepatic damage. Delusions are active after 12 weeks of treatment with clozapine.ConclusionsPsychiatric disorders and liver illnesses are entangled in multiple ways. Screening for liver diseases is essential in order to prevent liver complications in patients receiving psychotropic medications. Further investigation of combinations of agents such as mood stabilizers and atypical antipsychotics may yield valuable insights into the potential of combination therapies to enhance clinical outcomes in patients with Severe Mental Disease.DisclosureNo significant relationships.

Long-term outcome of liver complications in patients with chronic HBV/HCV co-infection after antiviral therapy: a real-world nationwide study on Taiwanese Chronic Hepatitis C Cohort (T-COACH).

The long-term outcome of hepatitis B virus (HBV) infection among patients dually infected with HBV and hepatitis C virus (HCV) remains unclear. We aimed to investigate the long-term liver outcomes of HBV/HCV-coinfected patients after antiviral therapy. A total of 11,359 chronically HCV-infected patients with interferon-based therapy were registered in a nationwide Taiwanese Chronic Hepatitis C Cohort. A propensity score matched (PSM) cohort of HCV mono-infected (n = 7020) and HBV/HCV (n = 702) co-infected patients by age, sex, and fibrosis was recruited for outcome analysis. The primary outcome was liver-related complications, including hepatocellular carcinoma (HCC) and liver decompensation during a mean follow-up period of 4.44years. Among HBV/HCV co-infected patients, patients without HCV-SVR had a significantly higher 10-year cumulative incidence of major liver-related complications than those with HCV-SVR. However, among patients with HCV-SVR in the PSM cohort, the risk of major liver-related complications, both HCC and liver decompensation, did not differ between HBV/HCV co-infected and HCV mono-infected patients. Similar results were observed among those without HCV-SVR. A substantial lower risk of major liver-related complications was found in HBV/HCV co-infected patients with HCV SVR and subsequent anti-HBV nucleot(s)ide analogues treatment. Overall, factors associated with major liver-related complications included age ≥ 65year-old, BMI ≥ 27kg/m2, FIB-4 ≥ 3.25, eGFR < 60ml/min/1.73m2, and non-HCV SVR, but not HBV co-infection. Interferon-based therapy reduced the long-term risk of major liver-related complications among HBV/HCV co-infected patients, as among HCV mono-infected patients. Nevertheless, post-HCV-SVR surveillance for major liver-related complications is mandatory among those high-risk groups.

Liver Complications Associated with Systemic Lupus Erythematosus

Although liver dysfunction is not considered the main organ pathology or prognostic factor in patients with Systemic Lupus Erythematosus (SLE), it is not uncommon during the course of SLE. Liver complications in patients with SLE may be caused by lupus hepatitis (SLE-related hepatitis); autoimmune liver diseases, such as Autoimmune Hepatitis (AIH) and Primary Biliary Cirrhosis (PBC); viral hepatitis; and drug-induced liver injury. Here, liver complications in patients with SLE are reviewed.

Prediction of Liver Complications in Patients With Hepatitis C Virus-Related Cirrhosis With and Without HIV Coinfection: Comparison of Hepatic Venous Pressure Gradient and Transient Elastography

Hepatic venous pressure gradient (HVPG) is the best indicator of prognosis in patients with compensated cirrhosis. We compared HVPG and transient elastography (TE) for the prediction of liver-related events (LREs) in patients with hepatitis C virus (HCV)-related cirrhosis with or without human immunodeficiency virus (HIV) coinfection. This was a retrospective review of all consecutive patients with compensated HCV-related cirrhosis who were assessed simultaneously using TE and HVPG between January 2005 and December 2011. We used receiver operating characteristic (ROC) curves to determine the ability of TE and HVPG to predict the first LRE (liver decompensation or hepatocellular carcinoma). The study included 60 patients, 36 of whom were coinfected with HIV. After a median follow-up of 42 months, 6 patients died, 8 experienced liver decompensations, and 7 were diagnosed with hepatocellular carcinoma. The area under the ROC curve (AUROC) of TE and HVPG for prediction of LREs in all patients was 0.85 (95% confidence interval [CI], .73-.97) and 0.76 (95% CI, .63-.89) (P = .13); for HIV-infected patients, the AUROC was 0.85 (95% CI, .67-1.00) and 0.81 (95% CI, .64-.97) (P = .57); and for non-HIV-infected patients, the AUROC was 0.88 (95% CI, .75-1.00) and 0.77 (95% CI, .57-.97) (P = .19). Based on the AUROC values, 2 TE cutoff points were chosen to predict the absence (<25 kPa) or presence (≥40 kPa) of LREs, thus enabling correct classification of 82% of patients. Our data suggest that TE is at least as valid as HVPG for predicting LREs in patients with compensated HCV-related cirrhosis with or without concomitant HIV coinfection.

Evaluation of factors associated with the nutritional mixture leading to liver complications in patients treated by means of parenteral nutrition at home

The major problem of total parenteral treatment consists in the balancing of the source and dose of the nutritional mixture, so as to not deepen malnutrition with a positive impact on the patients' organism. The aim of the study was to evaluate selected factors that induce hepato-biliary complications in patients treated by means of parenteral nutrition at home. The retrospective study comprised 70 patients with biochemistry performed every three months. Considering statistical analysis patients were allocated to four groups, depending on the period of treatment. Group A analysis results were based on the activity of aminotransferases, group B on the activity of bilirubin. Both groups A and B were additionally divided into group I where we assigned normal values of control lab results, and group II with improper results after treatment. Differences between groups Ia vs IIa were presented on the basis of the daily supply of glucose: mean- 2.52 vs 3.49 g/kg (p=0.000003), glucose/lipids ratio: mean- 3.76 vs 4.90 g/kg (p=0.0001), daily non-protein energy: mean- 16.73 vs 21.06 kcal/kg (p=0.0001). Differences between groups Ib vs IIb were presented on the basis of the daily supply of glucose: mean- 2.76 vs 3.46 g/kg (p=0.0007), glucose/lipids ratio: mean- 3.98 vs 5.13 g/kg (p=0.01), daily non-protein energy: mean-17.96 vs 20.36 kcal/kg (p=0.04). Based on the above-mentioned analysis the main goal in the prevention of hepatic complications should lead to the reduction of the dose of glucose. Increased glucose supply leads to increased number of hepato-biliary complications. Based on obtained results we were able to conclude that in case of liver complications associated with parenteral nutrition, proper management consists in the modification of nutritional mixtures (reduction in the daily glucose supply and change in the proportions of extra-protein energy). Such management has the greatest clinical effect. When determining the composition of the nutritional mixture one should adjust the glucose supply, so as to offset both sources of extra-protein energy.

Differential expression of haptoglobin isoforms in chronic active hepatitis, cirrhosis and HCC related to HBV infection

The three main complications of hepatitis B virus (HBV) infection are chronic active hepatitis (CAH), liver cirrhosis, and hepatocellular carcinoma (HCC). The aim of this study was to identify differentially expressed serum proteins among the three liver complications in patients with HBV infection. Differentially expressed proteins have been shown to be potential biomarkers for disease diagnosis, prognosis and therapy guidance. Two-dimensional polyacrylamid gel electrophoresis (2DE) combined with liquid chromatography tandem mass spectrometry (LC-MS/MS) was performed on sera from CAH, cirrhosis and HCC patients with HBV infection, as well as those obtained from healthy individuals. Of 54 differentially expressed (≥1.5-fold and p<0.05) protein spots, 35 spots were identified by LC-MS/MS. The identified spots correlated to 13 proteins. The proteins included haptoglobolin α-2 and βisoforms, haptoglobin cleaved β isoforms, retinol-binding protein, transthyretin, ficolin, leucine-rich-α-2-glycoprotein, α-1-antitrypsin and clusterin. Of particular interest is the significant increase of haptoglobin α-2 isoforms in HCC patients compared to cirrhosis ones. In contrast, a significant decrease of the isoforms was noted among cirrhosis patients.

S1871 The Association of Low Level of Both Vitamin a and Retinol Binding Protein With the Liver Complications in Patients With Primary Sclerosing Cholangitis

Background/Aims: There has been increased interest in the potential role of B cells and antimitochondrial antibodies in PBC. Indeed a new paradigm in PBC includes the potential of B cells to act as both regulatory elements and as components of the inflammasone induced by apoptosis of biliary cells. We submit that a rigorous dissection of the inflammatory infiltrate in PBC will provide further insight on these issues. Materials and Methods: We took advantage of well-characterized Mabs to CD3, CD4, CD8, CD20, CD38, CD56, CD68, and pan-keratin antigens, and immunohistochemistry (IHC), to study the distribution of liver infiltrating CD38-positive plasma cells in 26 consecutive patients with PBC (AMA positive in 20 and negative in 6), all of whom had detailed staged clinical data. All data was “blindly” evaluated. We simultaneously studied 10 ageand gender-matched patients with chronic hepatitis C as a control. Results: Noteworthy within the IHC data was the presence of an intense coronal arrangement (CR) of CD38-positive cells around interlobular bile ducts, generally in specimens with chronic non-suppurative destractive cholangitis (CNSDC). In contrast, CD20-positive B lymphocytes (precursor cells of plasma cells) were found scattered and/or aggregated within the lymphoplasmocytic infiltration. Such CD20positive B cells also occasionally formed follicle-like aggregations but importantly were not observed in the proximity of CNSDC. PBC patients with CR demonstrated significantly higher titers of AMA (119.5±16.1 vs. 59.7±17.1, p=0.018) and lower levels of total cholesterol (TC) (195.1±9.0 vs. 223.6±9.6, p=0.04) than those without CR. Interestingly the CR correlated with titer of AMA (r=0.46), IgM (r=0.32), the presence of CNSDC (r=0.32) and inversely with age (r=-0.37), γ-GTP (r=-0.38) and TC (r=-0.41). In contrast, CD4and CD8-positive T lymphocyte infiltration was noted either in proximity of, or within the degenerated cholangioepithelium, suggesting the participation of these cells in the destructive processes of interlobular bile ducts. No CR was found in control subjects. Conclusion: The presence of CD38+ plasma cells surrounding biliary epithelium has clinical and serologic significance; further it correlates with disease progression exemplified by TC decrease and the development of florid duct lesions. These data further highlight the functional significance of B cells/ plasma cells; it also reflects a multilineage loss of tolerance in PBC. We submit that study of B cells in PBC should go beyond simple measurement of AMA titer and include rigorous phenotypical and functional dissection of the liver specific B cell lineage populations.

Factors Associated with Progression to Hepatocellular Carcinoma and to Death from Liver Complications in Patients with HBsAg-Positive Cirrhosis

Hepatitis B viral markers and liver tests were used as predictors for development of hepatocellular carcinoma and progression to end-stage liver disease in 128 cirrhosis patients with hepatitis B. During a median follow-up of 63.5 months, 28 patients (21.9%) developed HCC and 36 (28.1%) died from non-HCC liver deaths. By multivariate analysis, independent predictors of HCC development and their hazard ratios were high alfa-fetoprotein (HR2.83, 95% CI 1.60-5.00, P = 0.0003), negative HBeAg (HR2.33, 95% CI 1.04-5.29, P = 0.04), and low alanine aminotransferase value (HR1.42, 95% CI 1.08-1.89, P = 0.02). Independent predictors of non-HCC liver deaths were HBeAg positivity (HR3.39, 95% CI 1.16-9.93, P = 0.02), decrease albumin (HR1.61, 95% CI 0.99-2.63, P = 0.05), decrease platelet count (HR2.54, 95% CI 1.03-6.25, P = 0.04), high ALT value (HR1.22, 95% CI 1.03-1.43, P = 0.02), and onset of encephalopathy (HR3.34, 95% CI 1.21-9.27, P = 0.02). HBeAg negativity, elevated AFP, and low ALT values predicted HCC development, while HBeAg positivity, abnormal liver tests, and low platelet counts identified patients with non-HCC liver deaths.